Myoendothelial Relations in the Conduit Coronary Artery of the Dog and Rabbit

Kristek, F; Gerová, M

doi:10.1159/000158928

Cited by 21 publications

(13 citation statements)

References 14 publications

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“…Together with ultrastructural evidence for myoendothelial couplings (Spagnoli et al, 1982;Taugner et al, 1984;Kristek & Gerova, 1992), these observations may support the hypothesis that the hyperpolarization is initiated in the endothelium and conducted to the underlying smooth muscle via low resistance electrical couplings or gap junctions (see, Beny & von der Weid, 1991). In support of an electrotonic conduction, the gap junction uncoupler, 1-heptanol, attenuated the Nw-nitro-L-arginine (L-NOARG)/indomethacin (IM)-resistant relaxation induced by bradykinin in porcine coronary arteries (Kiihberger et al, 1994).…”

Section: Introductionsupporting

confidence: 58%

Role of potassium channels in endothelium‐dependent relaxation resistant to nitroarginine in the rat hepatic artery

Zygmunt

Högestätt

1996

British J Pharmacology

197

182

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1 In the presence of indomethacin (IM, 1OiM) and Nw-nitro-L-arginine (L-NOARG, 0.3 mM), acetylcholine (ACh) induces an endothelium-dependent smooth muscle hyperpolarization and relaxation in the rat isolated hepatic artery. The potassium (K) channel inhibitors, tetrabutylammonium (TBA, 1 mM) and to a lesser extent 4-aminopyridine (4-AP, 1 mM) inhibited the L-NOARG/IM-resistant relaxation induced by ACh, whereas apamin (0.1-0.3 gM), charybdotoxin (0.1-0.3MM), iberiotoxin (0.1 MM) and dendrotoxin (0.1 Mm) each had no effect. TBA also inhibited the relaxation induced by the receptor-independent endothelial cell activator, A23187. 2 When combined, apamin (0.1 MM)+charybdotoxin (0.1 uM), but not apamin (0.1 MM)+iberiotoxin (0.1 Mm) or a triple combination of 4-AP (1 mM) + apamin (0.1 MM) + iberiotoxin (0.1 Mm), inhibited the L-NOARG/IM-resistant relaxation induced by ACh. At a concentration of 0.3 gM, apamin + charybdotoxin completely inhibited the relaxation. This toxin combination also abolished the L-NOARG/ IM-resistant relaxation induced by A23187. 3 In the absence of L-NOARG, TBA (1 mM) inhibited the ACh-induced relaxation, whereas charybdotoxin (0.3 MM)+ apamin (0.3 gM) had no effect, indicating that the toxin combination did not interfere with the L-arginine/NO pathway. 4 The gap junction inhibitors halothane (2 mM) and 1-heptanol (2 mM), or replacement of NaCl with sodium propionate did not affect the L-NOARG/IM-resistant relaxation induced by ACh.5 Inhibition of Na+/K+-ATPase by ouabain (1 mM) had no effect on the L-NOARG/IM-resistant relaxation induced by ACh. Exposure to a K+-free Krebs solution, however, reduced the maximal relaxation by 13% without affecting the sensitivity to ACh. 6 The results suggest that the L-NOARG/IM-resistant relaxation induced by ACh in the rat hepatic artery is mediated by activation of K-channels sensitive to TBA and a combination of apamin+charybdotoxin. Chloride channels, Na+/K+-ATPase and gap junctions are probably not involved in the response. It is proposed that endothelial cell activation induces secretion of an endothelium-derived hyperpolarizing factor(s) (EDHF), distinct from NO and cyclo-oxygenase products, which activates more than one type of K-channel on the smooth muscle cells. Alternatively, a single type of K-channel, to which both apamin and charybdotoxin must bind for inhibition to occur, may be the target for EDHF.

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Section: Introductionsupporting

confidence: 58%

Role of potassium channels in endothelium‐dependent relaxation resistant to nitroarginine in the rat hepatic artery

Zygmunt

Högestätt

1996

British J Pharmacology

197

182

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“…Exogenously applied K + often failed to evoke any relaxation in these arteries, whereas CPA always evoked EDHF responses, arguing against an important role for this ion as an EDHF in this vascular bed. Thus given the physical and functional evidence we provide for MEGJs, it is conceivable that direct cell-cell coupling of hyperpolarizing current (or a factor) could underlie the EDHF response, as suggested by others [13, 40, 41, 42, 43, 44]. It is not possible to test this pharmacologically, as there are no generally accepted, selective MEGJ uncouplers.…”

Section: Discussionmentioning

confidence: 90%

Myoendothelial Gap Junctions May Provide the Pathway for EDHF in Mouse Mesenteric Artery

et al. 2003

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Endothelium-dependent hyperpolarization of vascular smooth muscle provides a major pathway for relaxation in resistance arteries. This can occur due to direct electrical coupling via myoendothelial gap junctions (MEGJs) and/or the release of factors (EDHF). Here we provide evidence for the existence of functional MEGJs in the same, defined branches of BALB/C mouse mesenteric arteries which show robust EDHF-mediated smooth muscle relaxation. Cyclopiazonic acid (CPA, 10 µM) was used to stimulate EDHF in arteries mounted under isometric conditions and constricted with phenylephrine. Simultaneous measurement of smooth muscle membrane potential and tension demonstrated that CPA caused a hyperpolarization of around 10 mV, reversing the depolarization to phenylephrine by 94% and the associated constriction by 66%. The relaxation to CPA was endothelium dependent, associated with the opening of Ca²⁺-activated K channels, and only in part due to the release of nitric oxide (NO). In the presence of the NO synthase inhibitor, L-NAME (100 µM), the relaxation to CPA could be almost completely inhibited with the putative gap junction uncoupler, carbenoxolone (100 µM). Inhibition of the synthesis of prostaglandins or metabolites of arachidonic acid had no effect under the same conditions, and small rises in exogenous K⁺ failed to evoke consistent or marked smooth muscle relaxation, arguing against a role for these molecules and ions as EDHF. Serial section electron microscopy revealed a high incidence of MEGJs, which was correlated with heterocellular dye coupling. Taken together, these functional and morphological data from a defined mouse resistance artery suggest that the EDHF response in this vessel may be explained by extensive heterocellular coupling through MEGJs, enabling spread of hyperpolarizing current.

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“…49,50 A close correlation exists between the expression of myo-endothelial gap junctions and the occurrence of EDHF-mediated responses. [51][52][53] Furthermore, the number of myo-endothelial gap junctions increases as the size of the artery decreases, 54,55 a phenomenon that parallels the contribution of the EDHF-mediated responses in endothelium-dependent relaxations. 56,57 In many blood vessels, blockers of gap junctions (glycyrrhetinic acid and some of its derivative such as carbenoxolone, HEPES and other taurine-based buffers and Gap peptides), partially inhibit or abolish EDHF-mediated responses.…”

Section: Gap Junctionsmentioning

confidence: 97%

Endothelium-Derived Hyperpolarizing Factor

Félétou

Vanhoutte

2006

ATVB

419

274

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Abstract-The endothelium controls vascular tone not only by releasing nitric oxide (NO) and prostacyclin but also by other pathways causing hyperpolarization of the underlying smooth muscle cells. This characteristic was at the origin of the denomination endothelium-derived hyperpolarizing factor (EDHF). We know now that this acronym includes different mechanisms. In general, EDHF-mediated responses involve an increase in the intracellular calcium concentration, the opening of calcium-activated potassium channels of small and intermediate conductance and the hyperpolarization of the endothelial cells. This results in an endothelium-dependent hyperpolarization of the smooth muscle cells, which can be evoked by direct electrical coupling through myo-endothelial junctions and/or the accumulation of potassium ions in the intercellular space. Potassium ions hyperpolarize the smooth muscle cells by activating inward rectifying potassium channels and/or Na ϩ /K ϩ -ATPase. In some blood vessels, including large and small coronary arteries, the endothelium releases arachidonic acid metabolites derived from cytochrome P450 monooxygenases. The epoxyeicosatrienoic acids (EET) generated are not only intracellular messengers but also can diffuse and hyperpolarize the smooth muscle cells by activating large conductance calcium-activated potassium channels. Additionally, the endothelium can produce other factors such as lipoxygenases derivatives or hydrogen peroxide (H 2 O 2 ). These different mechanisms are not necessarily exclusive and can occur simultaneously.

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Myoendothelial Relations in the Conduit Coronary Artery of the Dog and Rabbit

Cited by 21 publications

References 14 publications

Role of potassium channels in endothelium‐dependent relaxation resistant to nitroarginine in the rat hepatic artery

Role of potassium channels in endothelium‐dependent relaxation resistant to nitroarginine in the rat hepatic artery

Myoendothelial Gap Junctions May Provide the Pathway for EDHF in Mouse Mesenteric Artery

Endothelium-Derived Hyperpolarizing Factor

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